Independent elaboration of steroid hormone signaling pathways in metazoans

Abstract

Steroid hormones regulate many physiological processes in vertebrates, nematodes, and arthropods through binding to nuclear receptors (NR), a metazoan-specific family of ligand-activated transcription factors. The main steps controlling the diversification of this family are now well-understood. In contrast, the origin and evolution of steroid ligands remain mysterious, although this is crucial for understanding the emergence of modern endocrine systems. Using a comparative genomic approach, we analyzed complete metazoan genomes to provide a comprehensive view of the evolution of major enzymatic players implicated in steroidogenesis at the whole metazoan scale. Our analysis reveals that steroidogenesis has been independently elaborated in the 3 main bilaterian lineages, and that steroidogenic cytochrome P450 enzymes descended from those that detoxify xenobiotics. evolution ͉ nuclear-receptor ligand ͉ steroidogenesis

Insights from the structure of estrogen receptor into the evolution of estrogens: Implications for endocrine disruption

“…Here, we investigate another unresolved question about the ER: the identity of the ligand(s) for the ancestral ER [3,7,18,21]. Phylogenetic analyses of lamprey and other vertebrate steroid receptors established that the ER was the ancestral steroid receptor [7].…”

“…CYP450s, 3 / 5-4 -HSD and 17 -HSD-type 2 catalyze the formation of vertebrate steroids from cholesterol [18,[51][52].…”

“…In particular, deacylcortivazol, which has a large substituent at the A ring and thus lacks a C3 ketone, has a 10-fold higher affinity for the GR than does dexamethasone [46]. The crystal structure of the GR-deacylcortivazol complex Lastly, conformational flexibility of the ligand-binding pocket in the ER and other nuclear receptors may have been important in the evolution of their response to oxysterols and vertebrate hormones from ancestral signals [3,18,20].…”

“…Although mollusks and annelids contain receptors with sequence similarity to the human ER [15][16][17], there is disagreement as to whether these protostome receptors diverged from a common ancestor of chordate ER [17], or if the similarity between protostome proteins and the chordate ER is an example of convergent evolution [18][19][20]. The pros and cons of this controversy are discussed in [17][18][19][20] and are not the focus of this paper.…”

11β-Hydroxysteroid dehydrogenase-type 2 evolved from an ancestral 17β-Hydroxysteroid dehydrogenase-type 2

“…Sea urchin, a basal deuterostome, contains 11 -HSD3A. There is no evidence for glucocorticoid receptors in sea urchin [25]. 11 -HSD3A is present in amphioxus and Ciona, while 11 -HSD1 and 11 -HSD2 are in the elephant shark.…”